Phase 2 clinical trial of attenuated Salmonella enterica serovar typhi oral live vector vaccine CVD 908-htrA in U.S. volunteers.

Salmonella enterica serovar Typhi strain CVD 908-htrA is a live attenuated strain which may be useful as an improved oral typhoid vaccine and as a vector for cloned genes of other pathogens. We conducted a phase 2 trial in which 80 healthy adults received one of two dosage levels of CVD 908-htrA in a double-blind, placebo-controlled, crossover study. There were no differences in the rates of side effects among volunteers who received high-dose vaccine (4.

Multiple acute stroke syndrome: marker of embolic disease?

Objective: To determine the frequency and etiologic significance of multiple acute ischemic lesions in stroke.

Background: Although patients may have more than one stroke during the course of their lives, acute ischemic stroke is usually thought of as a single event. Using diffusion-weighted imaging (DWI), an MRI technique that detects ischemic injury within minutes after onset, we have often observed multiple acute ischemic lesions.

Silent functional magnetic resonance imaging demonstrates focal activation in rapid eye movement sleep.

Functional imaging of human sleep has been performed with nuclear medicine methods, but MRI has been difficult to implement, in part because of the noise associated with echo-planar imaging as well as the difficulty in reading physiologic signals in the MRI environment. We describe a silent MR sequence that can record brain activation over many hours with simultaneous acquisition of an EEG. This shows activation of occipital cortex and deactivation of frontal cortex during REM sleep, in agreement with previous studies using other techniques.

Echo-planar functional MR imaging of epilepsy with concurrent EEG monitoring.

Background And Purpose: The role of functional MR (fMR) imaging in the evaluation of patients with epilepsy has not been systematically studied. Our purpose was to identify the fMR correlates of interictal epileptiform discharges.

Methods: Twenty patients with epilepsy and frequent interictal discharges were studied with concurrent EEG monitoring on a 1.

Magnetic resonance imaging of the thorax. Past, present, and future.

Magnetic resonance is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

Relationship between motion of coronary arteries and diaphragm during free breathing: lessons from real-time MR imaging.

Objective: Diaphragmatic navigators are frequently used in free-breathing coronary MR angiography, either to gate or prospectively correct slice position or both. For such approaches, a constant relationship between coronary and diaphragmatic displacement throughout the respiratory cycle is assumed. The purpose of this study was to evaluate the relationship between diaphragmatic and coronary artery motion during free breathing.

Pulmonary disorders: ventilation-perfusion MR imaging with animal models.

Purpose: To demonstrate the capability of magnetic resonance (MR) imaging to assess alteration in regional pulmonary ventilation and perfusion with animal models of airway obstruction and pulmonary embolism.

Materials And Methods: Airway obstruction was created by inflating a 5-F balloon catheter into a secondary bronchus. Pulmonary emboli were created by injecting thrombi into the inferior vena cava.

Central nervous system abnormalities assessed with prenatal magnetic resonance imaging.

Objective: To determine the frequency at which magnetic resonance imaging (MRI) provides additional information in fetuses with suspected central nervous system (CNS) abnormalities on ultrasound.

Methods: Between May 1, 1996, and March 26, 1999, 83 women with 90 fetuses (including seven sets of live twins) had 91 ultrasonographic and MRI examinations of the fetal CNS. Eight women were studied twice, one for two different indications.

Quantitative assessment of pulmonary perfusion with dynamic contrast-enhanced MRI.

The feasibility of qualitative assessment of pulmonary perfusion using dynamic contrast enhanced MRI with ultra-short TE has recently been demonstrated. In the current study, quantitative analysis was attempted based on the indicator dilution principle using a pig model of pulmonary embolism. The results were compared with the absolute pulmonary perfusion obtained with colored microspheres.

Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination.

CVD 103-HgR is a live oral cholera vaccine strain constructed by deleting 94% of the gene for the enzymatically active A subunit of cholera toxin from classical Inaba Vibrio cholerae O1 569B; the strain also contains a mercury resistance gene as an identifying marker. This vaccine was well tolerated and immunogenic in double-blind, controlled studies and was protective in open-label studies of volunteers challenged with V. cholerae O1.

Lack of prophylactic efficacy of an enteric-coated bovine hyperimmune milk product against enterotoxigenic Escherichia coli challenge administered during a standard meal.

Orally administered bovine immunoglobulins with specific activity against colonization factors of enterotoxigenic Escherichia coli (ETEC) could provide passive protection against ETEC challenge in volunteers. Twenty healthy adult volunteers ingested either a placebo or a partially enteric-coated preparation of bovine immunoglobulins with activity against the colonization factor antigens CFA/I, CS3, and CS6 and then were challenged with ETEC strain E24377A (CS1+, CS3+) administered with a standard meal. There was no difference in the incidence or severity of diarrhea among the 10 volunteers who received the bovine immunoglobulins and the 10 who received placebo.

The ischemic penumbra: operationally defined by diffusion and perfusion MRI.

Background: Identifying tissue at risk for infarction is important in deciding which patients would benefit most from potentially harmful therapies and provides a way to evaluate newer therapies with regard to the amount of ischemic tissue salvaged.

Objective: To operationally define and characterize cerebral tissue at risk for stroke progression.

Methods: We retrospectively selected 25 patients with an acute onset of a hemispheric stroke from our database who had undergone a combination of two diffusion-weighted MRI studies and a perfusion-weighted MRI study.

First-pass renal perfusion imaging using MS-325, an albumin-targeted MRI contrast agent.

Rationale And Objectives: MR angiography is proving to be a useful clinical study for the diagnosis of vascular disorders of renal arteries. However, its utility in terms of stenosis characterization is still limited. Renal perfusion could provide supplemental information that could allow for a comprehensive evaluation of renal artery stenosis by MR imaging.

Magnetic resonance T2* measurements of the normal human lung in vivo with ultra-short echo times.

The objective of this study was to measure T2* values of the normal human lung in vivo during breathhold using a rapid gradient-echo sequence with ultra-short echo times (TE). A sagittal slice of the right lung was imaged in six volunteers with various TE ranging from 0.5 ms to 5 ms using a clinical 1.

Phase 1 safety and immune response studies of a DNA vaccine encoding hepatitis B surface antigen delivered by a gene delivery device.

This study was designed to determine the safety and immunogenicity in volunteers of a DNA vaccine consisting of a plasmid encoding hepatitis B surface antigen delivered by the PowderJect XR1 gene delivery system into human skin. Seven healthy adult volunteers received two immunizations at one of three forces of delivery on day 0 and 56. The vaccine was well tolerated.

Echoplanar MR imaging for ultrafast detection of brain lesions.

Objective: We retrospectively evaluated the use of echo-planar imaging for ultrafast detection of brain lesions.

Materials And Methods: In our retrospective study, 61 patients were imaged with the following echo-planar sequences: single-shot proton density-weighted, single-shot T2-weighted, single-shot T2-weighted high-resolution, multishot proton density-weighted, and multishot T2-weighted. Lesions revealed in these patients ranged from 0.

Ventilation-perfusion MR imaging of the lung.

The assessment of regional ventilation in human lungs is important for the diagnosis and evaluation of a variety of pulmonary disorders, including pulmonary emphysema, diffuse lung disease (e.g., sarcoidosis, and pulmonary fibrosis), lung cancer, and pulmonary embolism.

MR imaging of pulmonary parenchyma with a half-Fourier single-shot turbo spin-echo (HASTE) sequence.

Objective: To evaluate the utility of a half-Fourier single-shot turbo spin-echo sequence (HASTE) at depicting lung parenchyma and lung pathology.

Methods And Patients: A HASTE sequence was applied to five normal volunteers and 20 patients with various pulmonary disorders to depict the lung parenchyma. Images were acquired with ECG-triggering and breath-holding.

Oxygen-enhanced magnetic resonance ventilation imaging of the human lung at 0.2 and 1.5 T.

Lung ventilation imaging using inhaled oxygen as a contrast medium was performed using both a 0.2 and a 1.5 T clinical magnetic resonance (MR) scanner in eight volunteers.

Resolution enhancement in single-shot imaging using simultaneous acquisition of spatial harmonics (SMASH).

Spatial resolution in single-shot imaging is limited by signal attenuation due to relaxation of transverse magnetization. This effect can be reduced by minimizing acquisition times through the use of short interecho spacings. However, the minimum interecho spacing is constrained by limits on gradient switching rates, radiofrequency (RF) power deposition and RF pulse length.

Obstetric MR imaging.

The surge in the development of fast magnetic resonance (MR) techniques has revolutionized our ability to image the pregnant patient and the fetus. Fast MR imaging techniques provide excellent resolution for imaging the maternal and fetal anatomies without the need for sedation. This article addresses the use of fast MR imaging techniques in the evaluation of the pregnant patient for adnexal masses, pelvimetry, hydroureteronephrosis of pregnancy, and placenta accreta.

Signal-to-noise ratio and signal-to-noise efficiency in SMASH imaging.

A general theory of signal-to-noise ratio (SNR) in simultaneous acquisition of spatial harmonics (SMASH) imaging is presented, and the predictions of the theory are verified in imaging experiments and in numerical simulations. In a SMASH image, multiple lines of k-space are generated simultaneously through combinations of magnetic resonance signals in a radiofrequency coil array. Here, effects of noise correlations between array elements as well as new correlations introduced by the SMASH reconstruction procedure are assessed.